Check all the pertinent facts before accepting a teaching post.


Extra-0ral photography.

Extra-0ral photography.


Deadly ray saves lives.

Deadly ray saves lives.


Prevention facts prove fads, fallacies worthless.


Clinic floor: arena for potential clash.


Coagulation tests help stop dental chair emergencies.


Are students ready to see changes in the profession?


Hypoglycemic patients require special precautions.


She pursues her career.

She pursues her career.


Rural America suffers appalling lack of dentists.


Student sees denture woes.

Student sees denture woes.


Hydrogen peroxide shows value of use.

Hydrogen peroxide shows value of use.


Dental education: a catharsis.

Dental education: a catharsis.


Pterygoid extension technic for maxillary reconstruction.


Psychological factors give rise to psychosomatic dental diseases.


Split denture for patients unable to 'open wide'.


Miniature radio can be hidden in tooth.

Miniature radio can be hidden in tooth.


Future of gold cloudy, but with a silver lining.


Relief of TMJ syndrome: 'a typical case history'.


'Visual impact carries message for patients.'.


High blood pressure in the dental practice.


Patient care perspectives.

Patient care perspectives.


DDPA reports. Report of the president.

DDPA reports. Report of the president.


Study in contrast: newly espoused, diverse approaches to prepaid care.


Use of denial in adolescents with bone cancer.


Recent developments in alloys for dental amalgams: their properties and proper use. Since the development more than ten years ago of a new type of amalgam alloy that will react with mercury without forming the unfavourable gamma2 (Sn7-8Hg) phase, several new alloy brands with a similar reaction pattern have been presented. This new generation of amalgam alloy is called non-gamma2 alloy as distinct from the conventional alloys. Three of the new alloys studied contain approximately three volume percent gamma2 and should be classified as modified concentional amalgams. The non-gamma2 amalgams may be characterized in the following way: (1) instead of gamma2 they contain a reaction product of copper and tin (Cu6Sn5), the so-called eta1 phase. (2) They are significantly more resistant to corrosion than the conventional amalgams but do in time produce sufficient solid corrosion products to seal the micro-fissures between filling and cavity walls. (3) When corroding, they do not release metallic mercury, and the solid corrosion products formed and precipitated on the free surface of the fillings seem relatively little resistant to the organic acids of the plaque. (4) Most of them have relatively low creep and tensile strength, but high compressive strength. (5) Clinically the non-gamma2 amalgams are remarkable for superior marginal integrity and, seemingly, also for improved persistence of surface lustre.


Exfoliative cytologic examinations in the early diagnosis of oral cancer. Oral cytology-in spite of the wide extension of the use of cytologic diagnostic methods in various branches of medicine was and is the subject of many controversies. Opinions concerning the reliability of oral exfoliative cytology differ but all agree upon one point, oral cytology is not a substitute for biopsy. The main value of oral exfoliative cytology seems to lie in the diagnosis of malignant tumours, but differs according to the stages of progression of the disease. Comparison of cytological and histological results in oral carcinomas according to various authors gave a false negative rate of between 0 and 31 per cent. Advanced oral carcinomas already arouse suspicion at clinical examination and indicate the need for a biopsy. Therefore, in spite of the frequent ulceration increasing the effectiveness of cytodiagnostics, the importance of exfoliative cytology in advanced tumours is diminished. Exfoliative cytology may act as an important diagnostic aid in early oral carcinomas with ulcerated surfaces, even in some clinically unsuspected cases malignancy can be detected. In multiple or extensive lesions the selection of the most suitable site for the biopsy is possible. In leukoplakia the effectiveness of cytology is still more subject to dispute, the rate of false negatives is reported as high as to 63-9 per cent. However, when taking the clinical type of leukoplakia into consideration, the erosive leukoplakias which are known to be more inclined to become malignant showed a 76-6 per cent reliability of cytodiagnosis.


Dental manpower needs in a developing community: a critical analysis of the West African scene. Research findings from various countries in West Africa clearly indicate that over 94 per cent of the adult population above 40 years of age suffer from periodontal disease in various degrees of severity. Those living in rural areas in West Africa, where dental health care services are not yet available, suffer more from this common disease. With progressive urbanization and changes in diet and eating habits, consumption of refined sugars is rising steeply (Table II) and dental caries has become a serious problem particularly in children from high socioeconomic homes. In Nigeria, DMF of 4-3 in the female and 3-9 in the male has been reported. There is general paucity of all cadres of dental manpower in all areas in West Africa. Dentist: population ratios range from 1 : 111,000 in Senegal to 1 : 1,935,000 in Tchad Republic (Table I). In Senegal, Ghana and Nigeria, Dental schools have been established and attempts are being made to meet the pressing need for dental manpower by the expansion of existing treatment centres and training institutions and the establishment of new ones (Table IV & V). Emphasis is laid on preventive dental health care programmes and the formal training of dental auxiliary personnel: Dental Therapists, Dental Hygienists, Dental Technicians and Dental Surgery Assistants, is taking place in Nigeria and Senegal. Dental Nurses/Therapists and Dental Hygienists if adequately trained in sufficient numbers can play an all-important role in the delivery of dental care and the execution of preventive programmes in the vast rural areas in the developing countries of West Africa with a population of over 122 million people.


Corticosteroids in diseases of the oral mucosa. The introduction of corticosteroids into oral medicine heralded a therapeutic advance, and substantial benefits have occurred from their use. Three topical steroids are being used currently in oral diseases, i.e. hydrocortisone hemisuccinate, triamcinolone in Orabase 0-1 per cent and betamethasone valerate 0-1 mg. The efficacy of these agents can be increased markedly if they are administered during the prodromal phase of ulceration, i.e. when lymphocyte activity is at its maximum. Therapeutic doses of all of them can be exceeded three times without impairing adrenal function. Nevertheless some of these preparations, as exemplified by topical medication, induced an unfortunate acute pseudomembranous candidiasis without any alteration in the plasma cortisol level. The routine examination and treatment of ulcers in the mouth should be a careful exercise helped by a good light source and a tongue spatula. Oral lesions affecting the soft tissues may be often difficult to diagnose, because of the rapid occurrence of secondary changes, such as maceration from moisture, abrasion by food and teeth, perhaps, and the existence of erosions and ulcerations from ruptured vesicles or bullae. Thus, diagnosis will depend not only on the grouping and distribution of lesion, but also on its subsequent behaviour. In some cases too there will be associated changes in the facial skin or elsewhere in the body.


What a public health planner wants from a periodontal assessment. Despite certain shortcomings, the assessment of caries using the DMF system of scoring is relatively simple, reproducible and provides some indication of treatment needs and the success of the treatment measures provided. No such index is yet in existence which will give similar information about the much more complicated disease processes involved in periodontal disease. Early attempts to introduce suitable indices included the PI index PMA and OHI indices with their modifications. These indices have performed best in assessing disease status but gave little or no information about treatment needs, treatment achievement or failure. WHO attempted to simplify the indices so that they could be scored on a present or absent basis, but clinical trials revealed the impossibility of maintaining comparability even on this level. Subsequent refinement of the procedure has produced improvements in the system including the recording of five categories of treatment needs, namely special oral hygiene instruction, prophylaxis and oral hygiene, instruction, periodontal therapy without extraction of teeth and periodontal therapy with extraction of some or all teeth. The system is described in the second edition of the WHO manual on Oral Health Surveys. There is still need for epidemiologists to further refine the criteria of periodontal disease and to identify the significance of the various signs of gingival and periodontal pathology.


Solarisation as an aid to bite mark analysis.


Where is woman's place.

Where is woman's place.


Bite marks in a murder case.

Bite marks in a murder case.


Worry, fear, and concern differentiated.


A follow-up on schizophrenics from various social subgroups seven years after initial hospitalization.


The impact of education on family change.


Patterns of crime among aged in Israel (a second phase report).


A note on the relative prevalence of phobic reaction in an Iranian psychiatric population.


Children in the hospital. (I) A note on some further psychological and cognitive distortions and implications of illness. (II) Indications for psychiatric liaison referral and consultation on the paediatric medical-surgical unit.


Requests for abortions--a psychiatrist's view.


The influence of background music on the behavior of brain-injured children.


Future directions in dental education at the Baltimore College of Dental Surgery.


A comparison of the corrosion of silver and titanium endodontic points.


Legislation affecting you. Legislative committee report.


Soluble antigens of Leptotrichia buccalis: their reaction with rabbit antisera.


Ad libs...

Ad libs...


An assessment of the "Aspir" endodontic irrigator/aspirator.


Dental restorative materials: a review of 1972 literature. Part II.


Some examples of extra root canals.

Some examples of extra root canals.


A practical approach to orthodontic treatment for the adult patient. The possibilities of treating malocclusions in adults are discussed and four cases of orthodontic treatment undergone by adults are described. Proper treatment can bring about improvements in most cases but it is neither necessary nor advisable to attempt a complete correction of all irregularities.


The study club as a means of continuing education.


Examples of healing following partial root canal filling.


The modular self-locking appliance system. Part 2. A variation in the combination technique.


Postgraduate training and graduate education in dentistry.


Third party programs.

Third party programs.


Oral malignacies in Israel--a ten year survey (1960-1969).


Third party interference in orthodontic practice.


The effect of two commercial antibacterial mouthrinses on plaque growth in vivo. An experimental study was designed to compare the claimed antibacterial effect of Betadine and Blend-a-med Fluid with the known plaque growth inhibiting effect of a 0.2% aqueous solution of chlorhexidine digluconate (Hibitane). Before the test perios for 5 days. During the following week they cleaned their teeth mechanically with toothbrush and toothpicks. For the third week the students were divided into three experimental groups. Following closely the manufacturers' recommendations, one group rinsed their mouths four times daily with 10 ml of Betadine, one group every 2 hours with a glassful of water containing 5-8 drops of Blend-a-med Fluid, and the control group twice daily with 10 ml of the 0.2% chlorhexidine solution. Mechanical cleaning of the teeth was not allowed during the experimental week. The Plaque Index scorings decreased significantly from the end of the no-hygiene to the end of the mechanical cleaning period. During the experimental period a further decrease of the mean P1I scores returned to the level recorded after the no-hygiene period. As neither Betadine nor Blend-a-med Fluid proved able to prevent plaque growth in vivo, there seems to be no indication for their use in treatment of gingivitis.


The possible pathogenesis of gingival recession. A histological study of induced recession in the rat. Stages in the pathogenesis of gingival recession were observed in rats in which pocketing had been induced by replacement of natural incisors with dental implants. Suitable conditions were thus created on the palatal aspect of the implant sockets for recession to occur. The recession process was examined at intervals by taking transverse serial sections. In the epithelial and connective tissues deep to the receding margin, morphological changes were seen which apparently lead to cleft formation and recession. These appeared to be associated with mononuclear cell infiltration of the connective tissue. The study suggests that gingival recession involves a localized inflammatory process which causes breakdown of connective tissue and leads to proliferation of the epithelium into the site of connective tissue destruction. Proliferation of the epithelial cells into the connective tissue brings about a subsidence of the epithelial surface, which is manifest clinically as recession.


The healing potential of the periodontal tissues following different techniques of periodontal surgery in plaque-free dentitions. A 2-year clinical study. A clinical trial was undertaken to study the healing capacity of the periodontal tissues following different modes of periodontal surgery in patients whose oral hygiene was professionally maintained at an optimal level. Fifty patients, distributed into five groups, participated in the study. Following an initial examination and presurgical treatment, the various patient groups were subjected to one of the following surgical procedures: 1) the apically repositioned flap operation including elimination of bony defects, 2) the apically repositioned flap operation including curettage of the bony defects but without removal of bone, 3) the "Widman flap" technique including elimination of bony defects, 4) the "Widman flap" technique including curettage of the bony defects but without removal of bone, 5) gingivectomy including curettage of the bony defects but without removal of bone. After surgery, all patients received oral hygiene instruction and professional cleaning of the teeth once every 2 weeks during a 2-year period. The results showed that periodontal disease can be cured and further destruction of the periodontal tissues avoided irrespective of the surgical technique utilized for pocket elimination. Different surgical techniques, however, promoted varying degrees of regeneration of the supporting tissues. The most favourable healing was obtained when resection of bone was avoided and when complete coverage of the alveolar bone was ensured.


Applications of the scanning electron microscope in dental medicine.


Free grafts of palatal mucosa on the lingual aspect of the mandible. A report of two cases. The importance of an adequate amount of keratinized and attached gingiva to maintain gingival health has been stressed by several authors (Friedman & Levine 1964, Lang & Löe 1972, Bernimoulin & Mühlemann 1973) and though the rationale for increasing the width of the gingiva applies equally well to both the lingual and the vestibular surfaces, only one report of a graft on the lingual aspect of the mandible in dentate patients has been found in the literature (Goldman & Cohen 1973). The object of this report is to describe the indications, the surgical procedure devised and the results obtained in two patients.


The causes of failure of restorations: a literature review.


Monitoring mastication.

Monitoring mastication.


The clinical assessment of two adhesive composite resins.


The pain dysfunction syndrome. Why females?


Comments on "a toxonomy for behavioral objectives in a dental school".


The Division of Dentistry, Department of Health, Education, and Welfare.


Future professional responsibilities of dental academicians.


Comparison of males and females in the dental admission testing program.


Expanded-duty auxiliaries (CON).

Expanded-duty auxiliaries (CON).


An educator's view of the education and utilization of auxiliaries.


Clinical dentistry today--excellence or mediocrity.


Skills analysis of a class I amalgam restoration in a mandibular right first molar. 1. Students changed their body position 32% more often than instructors during amalgam condensation. 2. Experienced instructors used 38% fewer strokes than students to condense the amalgam. 3. On the average, instructors used 65% less time per condensation stroke than students. This was not due to ability to move the instrument more quickly, since both students and instructors had similar minimum stroke times, but rather to the fact that instructors performed slowly less often. 4. The upstroke during condensation required nearly the same time for both students and instructors (an eight percent difference). It was the downstroke that was greatly different (a 96% difference). 5. Instructors repeated condensation strokes 22% more often than students, working more systematically with less "jumping around" in the cavity. 6. The total number of carving strokes was not related to experience. 7. Students repeated carving strokes more often than instructors. 8. Students and instructors tended to use the same length of strokes in carving. 9. There was a noticeable difference between instructors and students in the method used to grasp the instruments.


Cell-mediated destruction of human leukemic cells by MHC identical lymphocytes: requirement for a proliferative trigger in vitro. These experiments have investigated cellular mechanisms involved in the generation of cellular immune responses to human acute leukemic blasts. Because normal human lymphocytes are not able to recognize immunologically, in vitro, lymphocytes from MHC identical siblings, the present studies have examined the in vitro proliferative and cytotoxic responses of normal lymphocytes to MHC identical AML and ALL blasts. In those cases where acute leukemic cells were unable to induce a proliferative response by MHC identical lymphocytes, the generation of effective anti-leukemic cytotoxicity required the addition of unrelated stimulating cells to the sensitization culture. In contrast, leukemic blasts that induced a proliferative response by MHC identical lymphocytes were also able to stimulate anti-leukemic cytotoxicity. This could be augmented by the addition of unrelated stimulating cells to the sensitization culture. The specificity of anti-leukemic cell cytotoxicity was demonstrated in all instances by simultaneous testing of putative killer cells on 51Cr leukemic blasts as well as 51Cr-labeled MHC identical phytohemagglutinin blasts or normal lymphocytes. Simultaneous sensitization to MHC identical leukemic blasts and unrelated stimulating lymphocytes did not invariably generate anti-leukemic cytotoxicity even when allogeneic cytotoxicity was observed; the absence of demonstrable suppressor activity in these nonreactive combinations suggested that some individuals may be specifically immunoincompetent, and thereby unable to generate effective anti-leukemic CML.


What is correct dental care?

What is correct dental care?


Occlusal concepts.

Occlusal concepts.


The countersuit and malpractice.

The countersuit and malpractice.


National preventive dentistry program announced by AFDH.


Editorial.

Editorial.


Periodontal pocket depths related to adjacent proximal tooth surface conditions and restorations.


The utilization of mobile dental units by United States dental schools.


Report on the University of Louisville's long range planning committee's survey.


Deep bite diagnosis and its role in general practice.


Differential diagnosis of internal and external root resorption.


Antibiotics that interfere with bacterial protein synthesis.


Effect of protein and sodium hypochlorite on endodontic instruments.


Endodontic dry-heat sterilizer effectiveness.


Report of the 33rd annual meeting of the American Association of Endodontists Hollywood, Fla April 28-May 2, 1976.


Maxillary carcinoma.

Maxillary carcinoma.


Paresthesia following endodontic treatment.


Diabetic ophthalmoplegia.

Diabetic ophthalmoplegia.


Aldosterone excretion rate in normal subjects and hypertensive patients.


Bone scintigraphy of patients with nasopharyngeal cancer.


Lithium carbonate in the treatment of affective disorders.


High cervical commissural myelotomy in the treatment of pain. High cervical myelotomy was carried out on 10 patients. Commissurotomy was performed at the C1-3 level by a combined procedure of deep electrocogulation and sharp splitting of the posterior columns. The immediate results were excellent in all patients, but relapse of pain took place shortly in six of them; there was apparently no relation with the location of pain. No long-term favourable results were observed in this series. Only three patients exhibited a well-defined band of mild hypalgesia from C2 to T 10 dermatome, but it lasted for only three to four weeks. Transient lower or four limb ataxia was observed in seven patients. Different pain conducting systems seem to be affected by commissural myelotomy, but not to a sufficient extent to give permanent or long-lasting relief of pain. The indications for high cervical myelotomy are very limited: this procedure should be considered only in patients with unilateral or bilateral arm and/or upper chest pain, respiratory impairment, and short life expectancy.


Considerations of the soft tissues of normal occlusal subjects with good face and Tweed triangle.


Effects of size of mix and trituration time on physical properties of amalgam.


Studies on non-eugenol system cement (I): On reactivity and yields between Zn(OH)2 and o-methoxy phenol, o-methoxy benzoic acid and o-ethoxy benzoic acid.


Studies on non-eugenol system cement (II). Examination on reaction products between Zn(OH)2 and o-methoxy phenol, o-methoxy benzoic acid and o-ethoxy benzoic acid by means of IR.


Anti prophylactic antibiotics.

Anti prophylactic antibiotics.


Surgeons' view on treatment of mucoepidermoid carcinoma.


The Education Opportunity Bank.

The Education Opportunity Bank.


Interpretation of aspiration tests in local anesthetic injections. Three young adult laboratory rabbits were anesthetized with a barbiturate and their abdominal cavities were surgically opened to expose a variety of blood vessels. A number of veins and arteries were penetrated with 25- and 27-gauge needles attached to standard dental aspirating cartridge-type syringes. Aspiration tests were performed and the results were recorded. No differences in the performance of aspiration were detected with the two gauges of needles. Where the aperture of the needle lay unobstructed and wholly within a vein greater than 1.5 mm in diameter or within any artery, it was impossible not to aspirate blood even with a peer technique. In certain circumstances, false-negative and misleading positive readings are possible. Recommendations for a clinically reliable aspirating technique have been given and four grades of positive result described. Absolutely infallible interpretation of results is impossible but, provided the aspirating technique itself is sound, intelligent evaluation of observed effects should result in very few errors of interpretation.


Cardiorespiratory effects of outpatient anesthesia for oral surgery: trichloroethylene-halothane. The cardiorespiratory effects of trichloroethylene supplementation of nitrous oxide-oxygen anesthesia, with simultaneous use of halothane at induction as needed, were studied in outpatient oral surgery patients undergoing dental extractions under general anesthesia. The technique produced no deleterious cardiovascular effects that could be attributed to the combined use of these agents. Elevations of blood pressure, stroke volume, and peripheral resistance indicated light anesthesia. The versatility of halothane combined with the absence of nephrotoxic and hepatotoxic breakdown products of trichloroethylene provides a satisfactory technique for outpatient oral surgery. The agents appear pharmacologically complimentary in that halothane lacks analgesic properties and postoperative shivering occurs, while induction with trichloroethylene is slow and tachypnea is a problem.


Efficacy of antibiotic prophylaxis in intraoral orthognathic surgery. To assess the effect of prophylactic use of antibiotics on the incidence of postoperative wound infection in intraoral orthognathic surgery, a group of 98 patients was classified in antibiotic and nonantibiotic subgroups. Antibiotic prophylaxis was used in 35 cases and was not used in 63 cases. The overall incidence of infection was 11.4% and 11.1%, respectively. The type of surgery performed made apparent but not statistically significant differences in the incidence of infection. Alveolar surgery patients had a 14.2% incidence with antibiotics and 4.7% incidence without antibiotics, while sagittal osteotomy patients had 8.3% and 26.3%, respectively. The infections that occurred were minor, easily treated, and did not result in any compromise in the predicted outcome of the surgical result. On the basis of the data gathered in this study, we conclude that antibiotic prophylaxis is contraindicated in alveolar surgery, and should not be used routinely in sagittal osteotomies.


Case 18, Part 2. Aneurysm of the internal carotid artery.


Comparison of a microcrystalline collagen preparation and gelatin foam in extraction wounds. A microcrystalline collagen preparation and a gelatin foam were compared relative to their effects on hemostasis and healing in molar extraction sockets in cats. The agents were essentially equivalent in both hemostasis and the inflammatory response that accompanied healing. Healing was slightly retarded in comparison to that seen in untreated control sockets in a previous study. It appears likely that the inflammatory response was caused by oral contamination, which is unavoidable in this type of procedure, rather than by the agents themselves.


Lack of tearing after Le Fort I osteotomy. An unusual complication of lack of tearing after a Le Fort type I osteotomy for maxillary retrusion has been presented. A definite cause for the complication can only be postulated. The possibilities of this problem occurring may be prevented by more delicate use of osteotomes in the separation of the pterygoid plates.


Histological studies of the effects of subperiosteally implanted sulfathiazole. The use of implanted sulfathiazole to obliterate undercut alveolar ridges has given good results. The mechanism whereby this drug effects this change has been investigated with dogs as experimental models. It was found that a fibroplastic proliferation occurred that was possibly due to an irritative stimulus on the periosteum.


Temporary loss of vision after postsurgical hypotension.


Halothane hepatitis with subclinical manifestations: report of case.


Superficial spreading melanoma of the buccal mucosa: report of case.


Oral lesions of granuloma inguinale.

Oral lesions of granuloma inguinale.


Modified acrylic splint for anterior maxillary osteotomies.


Desmoplastic fibroma of the mandible in a 3-year-old child. A 3-year-old white girl was seen because of an enlarging mass in the left side of the mandible. The mass was 10 cm in diameter and the entire left hemimandible was involved. Examination of tissue after incisional biopsy showed desmoplastic fibroma. Surgical removal of the tumor required a hemimandibulectomy. The mandible was replaced immediately with a stainless steel mesh prosthesis with an acrylic condyle. A year later, there was no evidence of recurrence. Though the mesh became exposed in one area, we believe that esthetics and function were best served by its use.


Calcifying odontogenic cyst: report of three cases.


Vitamin E and periodontal disease.

Vitamin E and periodontal disease.


A clinical study of healing in humans following the excisional new attachment procedure. The excisional new attachment procedure was used to treat 75 suprabony pockets on 32 teeth in 9 patients. One-year postoperative measurements demonstrated an overall mean pocket reduction from 4.7 mm to 2.0 mm, of which 2.1 mm (77%) was new attachment and 0.6 mm was recession. Average amount of new attachment and percentage of new attachment were greatest on the midlingual surfaces of the teeth treated in this study. The results of this study showed the excisional new attachment procedure to be a simple, effective, and predictable procedure for achieving pocket elimination by means of a clinical new attachment of the gingival tissues in suprabony pockets.


Lichen planus of the gingiva.

Lichen planus of the gingiva.


A quantitative measurement of bacteremia and its relationship to plaque control. Despite the improvement in the patients' oral hygiene, there was no significant decrease in the frequency of bacteremia. There was no significant difference in bacteremia between brushing, flossing, or deplaquing either before or after initial periodontal preparation and plaque control in 21 healthy subjects. Utilizing more sophisticated bacteriologic techniques for the cultivation of obligate anaerobes, a relatively high frequency of anaerobic bacteremia was found.


Light and electron microscopic observations of osteoclastic alveolar bone resorption in rats monoinfected with Actinomyces naeslundii. Alveolar bone destruction in rats monoinfected with Actinomyces naeslundii proceeds via osteoclastic resorption. The osteoclastic activity is discontinuous, i.e. short periods of vigorous osteoclastic activity are followed by longer periods of inactivity during which the alveolar crest may be covered with osteoblastic cells or in many cases devoid of bone cells. The net effect in the monoinfected rats is rapid bone loss. Periods of osteoclastic activity were associated with dense inflammatory infiltration of the interdental tissue, ulceration of col epithelium and the presence of large adherent plaques of Actinomyces. Ultrastructural examination revealed uninuclear as well as multinuclear osteoclasts. These cells contained numerous mitochondria, abundant Golgi apparatuses, and well developed ruffled borders indicating that they were physiologically active in bone resorption.


Model surgery - a method for constructing a stable, accurate index.


Microstructure of amalgam surfaces.

Microstructure of amalgam surfaces. The polished amalgam surface was smoother than the burnished and the carved surfaces. The burnished surface was smoother than the carved surface. The granular structures on the burnished amalgam surface were found to be of tin-mercury alloy. Polishing appears to be the best finishing technique for amalgam restorations, and there is no substitute for it.


A magnetically retained interim maxillary obturator. A technique has been presented for the fabrication of a sectional interim maxillary obturator with retention augmented by a magnet. A tonogram revealed a 32 per cent decrease in hypernasality during speech when the prosthesis was worn (Fig. 12). The positive locking and continuous retentive quality of the prosthesis provided by the magnet permitted normal speech and mastication as well as an improved psychologic state during a very trying rehabilitation period.


Loosening adjustments for Hanau series of articulators.


Acute infectious gastroenteritis: recent advances pertinent to primary care practice.


The remodeling of the edentulous mandible. In a sample of mandibles having complete or nearly complete loss of dentition, the left half of each mandible was serially sectioned. The entire perimeter of each section was analyzed for the distribution of resorptive and depository periosteal surfaces, and from this information, the fields of remodeling were mapped for the mandible as a whole. The most common patterns of combined resorption-deposition and the range of variations were then determined. The over-all distribution of remodeling fields in the edentulous mandible differs markedly from that in the young, growing mandible. In most of the edentulous specimens, the surface of the basal bone on both the medial and lateral sides of the corpus is of a depository nature. The overlying alveolar regions on both the lingual and buccal sides, however, are characteristically resorptive. Significantly, the placement of the reversal line between the alveolar resorptive and the basal depository areas is much lower (i.e., at the level of the mental foramen) on the buccal side. Except for its inferior part, the lateral side of the ramus tends to be largely resorptive in character, and the posterior half of the lingual side also tends to be resorptive. Unlike the child's mandible, the posterior border of the ramus is resorptive, and the posteroanterior dimension of the ramus (not the whole mandible) becomes reduced and narrowed in conjunction with resorption along the anterior border. However, the amount removed from the anterior ramus is actually added to the dimension of the corpus, which becomes longer. Further, removal from the posterior ramus border does not affect the over-all length of the mandible unless condylar reduction is also involved. Also, over-all arch length is not decreased, because the surface of the mental protuberance is retained as a depository type of field (or at least does not become actively resorptive). The corpus-ramus angle (not gonial angle) is increased in the antegonial region. Because of the opening of this angle, over-all mandibular length as well as arch length is increased. In about half of the specimens, arch width was not decreased, because the lateral side of the corpus is usually of a depository nature. Notching of the anterior side of the condylar neck and the inferior part of the anterior ramus border is associated with resorptive fields in these regions, changes that are presumed to be a consequence of pressure contacts made with the articular tubercle and the maxillary tuberosity, respectively, in conjunction with a forward rotation of the whole mandible. The inferior direction of corpus realignment relative to the basal part of the ramus also increases the notching effect in the antegonial region, an effect augmented by the presence of the resorptive field in the notch itself. Certain specific variations commonly occur in several major regions of the mandible on both the lateral and medial sides...


Office management of the failing kidney.


Cloverleaf bladder.

Cloverleaf bladder.


Dental prepayment.

Dental prepayment.


Measles epidemic in New Jersey. Vaccine efficacy study in a well-protected population.


Allergy/immunology and the nervous system.


Diabetes education -- needs for the patient and professionals.


The spleen in Friend leukemia. I. Prolonged survival of leukemic mice after autoimplantation of spleen tissue. Friend virus infection of susceptible mice led rapidly to fulminant erythroleukemia and death. Subcutaneous implantation of leukemia spleen bits into splenectomized normal animals led to their early death from Friend leukemia. In contrast, bits of leukemic spleen implanted sc into splenectomized leukemic mice prolonged the survival of these animals. Concomitant with this survival was a reversal of the virus-induced immunosuppression and an increase in the levels of circulating, neutralizing, antivirus activity. This marked difference in response to leukemic spleen implants by leukemic as compared to normal mice reflected previous contact of the former with Friend Virus. Our studies indicated that the Friend virus-infected mouse mounted a resistance to the virus infection, which under certain conditions is capable of reversing the disease process.


The effect of calcium sucrose phosphates chewing gum on caries incidence in children.


WDS number one...again!

WDS number one...again!


Cytotoxicity of antisera to a myelogenous leukemia cell line with the Philadelphia chromosome. Rabbit antisera to myelogenous leukemia (ML) cells were raised; ML cells from line K-562 that has the Philadelphia (Ph) chromosome were used as antigen. Antibodydependent, complement-mediated cytotoxicity was demonstrated by the trypan blue test and Cr release assay for cultured ML cells, whereas no cytotoxicity was demonstrated for cells from B (SB) and T (MOLT 4) lymphoblastoid cell lines. The antisera showed no cross-reactivity for normal human peripheral leukocytes or purified granulocytes. A low level (less than 8%) of cytotoxicity was directed against cell membrane associated fetal bovine serum proteins. Absorption of the immune serum with normal human bone marrow cells of first trimester human whole embryo cells reduced the cytotoxic titer to a similar extent; this suggested the possibility of crossreactivity between ML cells and fetal antigen(s). However, the ML antigen(s) was unrelated to carcinoembryonic antigen (CEA), since absorption with CEA had no effect on the serum cytotoxic titer. The anti-ML sera were cytotoxic for cells taken from 10 patients with chronic myelogenous leukemia and from 3 with acute myelogenous leukemia. In contrast, the leukocytes of 1 of 4 patients with acute lymphocytic leukemia, and 3 of 7 with chronic lymphocytic leukemia shared similar antigenic determinants as demonstrated by cytotoxicity tests. The significance of the cross-reactivity of some lymphatic and ML cells may be the result of the use of rabbit sera that did not distinguish antigens common to both granulocytic and lymphocytic cells, or it may reflect an "immature" or "blastic" antigen present on many leukemia cells.


Are you paying enough?

Are you paying enough?


The spleen in Friend leukemia. II. Nonleukemic nature of spleen stroma. Pieces of Friend leukemic spleens implanted sc into mice regenerated into normal-appearing spleens if animals were protected against the leukemia. In unimmunized animals, the implant regenerated normally, but was subsequently infiltrated by leukemia cells. This leukemia cell infiltration required at least 30% stromal regeneration of the implant. The hematopoietic regeneration was primarily a repopulation with cells from the host animal, not with cells indigenous to the donor spleen. The development of the implant, whether normal or leukemic, was retarded by the presence of the host spleen, whether leukemic or normal. These studies strongly suggested that the stromal cells of the spleen are not directly involved in the virus-induced leukemic process but acted as supporting structure for the malignant cells.


Dental practice management and taxes.

Dental practice management and taxes.


An outline for the implementation of a school preventative dentistry program.


Dental insurance negotiations.

Dental insurance negotiations.


Letters to the editors.

Letters to the editors.


President's message UEINT = unite or untie.


Wisconsin Dental Service--another year? or a new year!


President's message. Women's auxiliary lauded.


Anti-trust--price fixing--licensing boards.


American dental health challenge of today promise of tomorrow.


Shuler speaks on specialty practice.

Shuler speaks on specialty practice.


Wisconsin dental manpower study. Part 1 of 2 parts.


President's message. Inaugural address to the house of delegates.


Wisconsin dental manpower study. Part 2 of 2 parts.


Survey of auxiliary salaries.

Survey of auxiliary salaries.


President's message: FTC challenges codes of ethics.


Aetna insurance and the railroad employees' national dental plan.


Continuing education: a viewpoint and invitation.


WDA visits Washington.

WDA visits Washington.


Editorials: "-and convulsions within.".

Editorials: "-and convulsions within.".


Address of the president.

Address of the president.


A resume of today's restorative procedures.


Histological pulp study using a new pulp capping agent.


Insurance plans available to T.D.A. members (Revised)*.


Bridging the communications gap.

Bridging the communications gap.


Health care today.

Health care today.


The challenge of oral cancer in Tennessee.


Dental health status and needs survey. Middle Tennessee Chest Disease Hospital.


Curriculum for: preparing the dental student to meet tomorrow's dental practice.


Cariostatic effects of fluoride mouthrinses in a fluoridated community.


Iodide mumps.

Iodide mumps.


In vitro evaluation of marginal leakage of a new resin sealer.


Squamous cell carcinoma of the gingivae.


Pancreatic carcinoma as a sequel to therapy of lymphoma. Development of a carcinoma in the pancreas of a young man who had five years previously undergone intensive radiotherapy and subsequent chemotherapy for treatment of a lymphoma suggests that induction of the second neoplasm occurred as the result of the therapy of the first. While definite proof of causality is lacking, a review of recent literature strongly suggests that the association noted in the patient described is more than serendipitous. Increased usage of high-dose radiotherapy, particularly in conjunction with chemotherapy, may be directly related, and it is imperative that such an association be kept in mind when such patients are seen in follow-up.


Levels of gamma-aminobutyric acid in the dorsal grey lumbar spinal cord during the development of experimental spinal spasticity.


Chronic myelogenous leukemia with an unusual karyotype: 46,XY,t(17q +; 22q-)


Studies in mice on the antagonism of (+)-amphetamine anorexia by alpha-methyl-p-tyrosine methyl ester HCl.


Acute pancreatitis. Initial roentgenographic signs.


Effect of bronchodilator agents on arrhythmia.


Oral estramustine phosphate. Prolonged therapy for advanced carcinoma of prostate.


Synthetic lac operator DNA is functional in vivo.


Improved mammography system.

Improved mammography system.


Electrocardiogram of the month. Ventricular rate.


Locating young children with learning problems. Orientation to educational pediatrics.


Transient hypertension. Associated with methadone intoxication.


Electrocardiogram of the month. Sinus tachycardia with a rate of 100 beats per minute.


Epidermoid cysts of spleen. Importance of identification.


Jaundice from pancreatic pseudocyst. Diagnosis by endoscopic retrograde cholangiography.


Heart failure and hypoglycemia.

Heart failure and hypoglycemia.


Drug approval process and FDA.

Drug approval process and FDA.


Preduodenal portal vein.

Preduodenal portal vein.


Thromboembolic phenomena. Following ambulatory varicose vein surgery.


Tuberculin sensitivity. Contacts of tuberculosis patients.


Building Meadowbrook Hospital.

Building Meadowbrook Hospital.


Gallium-67 citrate scintigraphy. Value in non-Hodgkin's lymphoma.


Electrocardiograms of the month.

Electrocardiograms of the month.


Polytetrafluoroethylene grafts for arteriovenous fistulae. Preliminary report.


Correlation conferences in radiology and pathology. Diarrhea and right lower-quadrant mass.


Pure red-cell aplasia. Associated with adenocarcinoma of stomach.


Spontaneous rupture of stomach in neonate.


Pneumothorax in Marfan's disease.

Pneumothorax in Marfan's disease.


Time of death.

Time of death.


"Unnecessary" surgery. Scientifically erroneous testimony in Moss subcommittee hearings.


External pterygoid myotomy for recurrent mandibular dislocation. Review of the literature and report of a case. Dislocation of the temporomandibular joint is a condition that requires immediate attention. Several conservative methods are effective in the treatment of the acute episode, but surgical treatment is indicated for chronic dislocation. Many, sometimes conflicting, procedures have been proposed for the surgical treatment of chronic dislocation. Comprehensive review and analysis of the literature reveals that this confusion is generated by a poor understanding of the etiology of chronic dislocation. External pterygoid myotomy is recommended as the surgical treatment of choice since it eliminates the forces responsible for pulling the mandible into the dislocated position. A case is presented to demonstrate the effectiveness of this procedure.


Maternal mortality study. 1970-1975.

Maternal mortality study. 1970-1975.


Radionuclide bone imaging in the surgical treatment planning of odontogenic keratocysts. Locally aggressive benign lesions of the jaws, such as odontogenic keratocysts and ameloblastomas, require complete excision in view of the high incidence of recurrence after incomplete surgical removal. Because of the limitations of conventional radiology as the sole technique for determining the extent of these lesions, the use of 99m-technetium-labeled bone-imaging agents is suggested. This method of defining the location of surgical margins is based on the agent's sensitivity as an indicator of subtle changes in bone metabolism. A case of an unusually large recurrent odontogenic keratocyst is presented in which the planning of the surgical procedure was predicated on the results of a bone scan of the jaws in addition to conventional radiology. This diagnostic procedure, especially when used in conjunction with conventional radiology, appears to be of considerable value in defining the extent of a variety of oral-maxillofacial bony lesions.


Mural odontogenic epithelial proliferations within the wall of a dentigerous cyst: their significance. A case of a dentigerous cyst with proliferating odontogenic epithelium in a 5-year-old black boy is presented. A controversy exists in the histologic diagnosis and surgical treatment of this lesion. The accuracy of the pathologic diagnosis is imperative, as it will determine to a great extent the surgical modality of treatment.


Sarcoidosis with mandibular involvement. Report of a case. A case of mandibular involvement in sarcoidosis is presented. The diagnosis was based on positive chest roentgenograms, involvement of superficial and mediastinal lymph nodes of epithelioid tubercles, negative tuberculin test, and negative results of an examination with respect to tubercle bacilli. Mandibular involvement was diagnosed tentatively roentgenographically and verified by histopathologic examination. The mandibular lesion was treated surgically, and the defect healed uneventfully after less than 1 year. Almost complete normalization of the pulmonary lesions had taken place after 2 years.


Congenital neutropenia. Report of a case and a biorationale for dental management. Congenital neutropenia is characterized by a marked decrease in or lack of circulating PMN's in children with no prior history of drug intake. The neutropenia is persistent and the clinical course is one of early onset of severe, recurrent, and eventually fatal infections. Bone marrow studies show a maturation arrest of neutrophilic precursors. Because of their greatly increased susceptibility to infection, patients with congenital neutropenia present a difficult dental management problem. A case of congenital neutropenia has been presented, as well as a biorationale for dental treatment. On the basis of reports in the literature, the following recommendations for the management of patients with congenital neutropenia are made: 1. The prevention and control of infection and the interception of dental disease before surgical intervention becomes necessary should be the overriding considerations in the management of patients with congenital neutropenia. 2. The carious breakdown of teeth should be prevented by the daily application of a 0.4 per cent stannous fluoride gel in addition to oral hygiene and limitation of sucrose intake. 3. Periodontal therapy should be palliative only, since alveolar bone loss is progressive despite frequent oral hygiene instruction and prophylaxis. The goal of periodontal therapy for patients with congenital neutropenia should therefore be a decrease in gingival inflammation to make the patient's mouth more comfortable and to slow down alveolar bone loss. Periodontal surgery is contraindicated. 4. Bacteremia and subsequent septicemia should be prevented since a minor infection can become life threatening in patients with congenital neutropenia. The patient should rinse for 30 seconds and the gingival sulci should be irrigated with a phenolated antiseptic mouthwash prior to all dental manipulations of the soft tissue. This will significantly reduce the incidence of bacteremia. 5. Surgery should be avoided if at all possible because of the high risk of post-operative infection. All surgery sholld be performed in the hospital, and the patient should be given antibiotics as determined by his physician. Primary closure should be done with fine polyglycolic acid sutures to reduce the chance of infection. If postoperative infection can be prevented, wound healing will progress normally despite the complete absence of PMN's.


Salivary IgA and serum IgG and IgA in recurrent aphthous stomatitis. Salivary flow rate and sIgA were measured in twenty-one patients suffering from recurrent aphthous stomatitis (RAS). Out of this group ten volunteered for continuous study. In these patients salivary IgA and serum IgA and IgG were measured every 3 days for 3 weeks. All parameters were in the physiologic range of healthy people. No correlation with the clinical condition of the patients was found.


Occurrence of epithelial dysplasia in oral leukoplakia. Analysis and follow-up study of 12 cases. The histologic material of 500 leukoplakia patients was analyzed in order to define the characteristics of epithelial dysplasia and to correlate the findings with the clinical data. Epithelial dysplasia was found in 120 cases (24 per cent) and was graded as mild, moderate, or severe. The occurrence of dysplasia was highest in the group of erosive leukoplakias. The majority of the severe dysplasias were found on the tongue and lips. Follow-up studies on sixty-eight leukoplakia patients with histologic dysplasia revealed carcinoma in nine cases (13.2 per cent) during the mean observation period of 6.3 years. Leukoplakias of the tongue showed the highest incidence of malignant change.


Clear-cell calcifying odontogenic tumor viewed relative to the Pindborg tumor.


Recurrent "non-Hodgkin's lymphoma presenting with gingival enlargement. Report of a case. A 66-year-old white woman with recurrent "non-Hodgkin's lymphoma" is discussed. Her initial manifestation of recurrent disease was gingival enlargement. We reviewed the oral manifestations of lymphoma and discussed the course of this patient's disease, with particular attention to the local treatment of the gingival enlargement.


Atypical benign migratory glossitis. Report of a case with histologic and electron microscopic evaluations. A case of benign migratory glossitis atypically confined to only one side of the tongue is presented. The diagnosis was confirmed by repeated histopathologic evaluation. Electron microscopic studies revealed a striking intimacy between sensory nerve processes and the basal lamina of the lingual epithelium.


The investigation of microleakage in root canal therapy. An electrochemical technique. An electrochemical technique employing zero-resistance ammetry is described for evaluating the quantity, rate, and areas permeated in the canal system of a root-filled tooth by 1 per cent potassium chloride. Single-rooted extracted teeth were root-filled by a vertical condensation gutta-percha technique. The teeth were coated from the cementoenamel junction to 3 mm. from the apex with a stopping-off medium, so that the apical foramen and the accessory canals in the area would play a role, but not the lateral canals in the gingival area. The teeth were placed in a potassium chloride solution. When the potassium chloride permeated the apical seal and reached a mild steel rod placed through the occlusal access opening extending 2 mm. into the coronal end aspect of the canal, corrosion of the steel was established and was measured for quantity and rate. This technique suggests the possibility of another pathway for tissue fluid to effect coronal dentinal discoloration. The technique also suggests a quantitative means of measuring apical sealing procedures.


A statistical analysis of anaerobic versus aerobic culturing in endodontic therapy. Asymptomatic teeth were cultured at four specific stages of endodontic therapy, yielding 148 paired samples. Half of the samples were incubated anaerobically with the use of a new medium, and half were incubated aerobically with the use of a commonly employed endodontic medium. The former proved to be significantly more sensitive in supporting microbial growth from root canals. The results indicate that an aerobic culturing technique alone is not sufficient to reflect the microbiologic status of the canal system.


Tomographic evaluation of 100 patients with temporomandibular joint symptoms. In this study the temporomandibular joints of 100 patients were examined radiographically. While the results leave many unanswered questions, studies of this type do contribute to an increase in the knowledge of this complex structure. It is anticipated that polycycloidal tomography will provide even greater knowledge of the bony components of the TMJ. More accurate, objective radiographic evidence will unquestionably allow us to approach subjective clinical evidence with greater confidence in relating these factors to diagnosis. Dentistry must recognize that the newer and more sophisticated methods must be utilized to evaluate pathologic changes or disease entities, such as temporomandibular joint dysfunction. A health profession must be provided with maximum information for total diagnosis.


Unusual foreign objects in pulp canals.

Unusual foreign objects in pulp canals.


Localization of objects in the anterior areas with a single Panorex radiograph. Impacted objects in the anterior dental region can be localized in a labial-palatal direction with a single Panorex film. Clark's rule is applied to the two views of the anterior area obtained. The technique is verified by means of a dry skull with lead markers in known positions, and two clinical cases are reported.


Posterior fusion.

Posterior fusion.


Deciduous impaction.

Deciduous impaction.


Battered child syndrome.

Battered child syndrome.


Food for thought.

Food for thought.


Dental floss! Eureka! What great stuff!

Dental floss! Eureka! What great stuff!


Interaction of drugs used in dentistry.

Interaction of drugs used in dentistry.


Construction of a hybrid col E1 plasmid carrying the gene for bacteriophage lambda repressor. A biologically active hybrid DNA molecule was constructed from plasmid Col E1 and the Eco R1 fragment of lambda DNA containing the gene for lambda repressor. The presence of this gene in the hybrid molecule was demonstrated genetically. The hybrid plasmid contains two closely located targets for restriction endonuclease Hind 111 in the integrated fragment. Thus, the plasmid may be used as a vector not only for Eco R1 fragments but also for Hind 111 fragments.


Fluoridation: statistical evaluation of data.


Women employees: the new laws.

Women employees: the new laws.


Integration of eukaryotic genes for 5S RNA and histone proteins into a phage lambda receptor. Highly purified HindIII restriction fragments of Xenopus laevis 5S DNA and of Psammechinus miliaris histone DNA have been covalently inserted into a derivative of phage lambda. This phage, genetically constructed by Murray et al. (1), contains only a single target for HindIII in the cI gene. Viable hybrid molecules were detected as clear plaque-forming phage after transfection of E. coli, the vast majority of which were shown by hybridization to be recombinants of the desired type. The lambdaSam7 mutation has been introduced into one hybrid phage containing histone DNA, thereby substantially increasing the yield of recombinant DNA.


Isolation, primary structure, and synthesis of alpha-endorphin and gamma-endorphin, two peptides of hypothalamic-hypophysial origin with morphinomimetic activity. The isolation and primary structure of two peptides with morphinomimetic activity, obtained from an extract of porcine hypothalamus-neurohypophysis, are described. The amino acid sequence of the two peptides, named alpha-endorphin and gamma-endophin, was determined by mass spectrometry and danxyl-Edman methods to be H-Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-OH and H-Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-OH, respectively. These correspond to the amino acid sequences present between residues 61 and 76 and residues 61 and 77 of the various beta-lipotropins. A third peptide also obtained in pure form in these studies was found to be an unstable salt of alpha-endorphin.


Role of subunit interfaces in the allosteric mechanism of hemoglobin. We calculate the surface area buried in subunit interfaces of human deoxyhemoglobin and of horse methemoglobin. A larger surface area is buried in deoxy- than in methemoglobin as a result of tertiary and quaternary structure changes. In both molecules the dimer-dimer interface is closepacked. This implies that hydrophobicity stabilizes the deoxystructure, the free energy spent in keeping the subunits in a low-affinity conformation being compensated by hydrophobic free energy due to the smaller surface area accessible to solvent.


Resonance enhanced coherent anti-Stokes Raman scattering. Resonance enhancement of coherent anti-Stokes Raman scattering due to the proximity of the laser frequencies to an electronic transition has been demonstrated for dilute solutions of diphenyloctatetrane in benzene. The Raman contribution to the third order susceptibility is shown to be complex near an electronic resonance and the resulting features of the coherent anti-Stokes Raman scattering spectra are discussed in detail. This work represents one step in the demonstration that the high signal to noise ratio, fluorescence rejection, and low average power levels of the coherent anti-Stokes Raman scattering experiment can be used to advantage in Raman studies of dilute solutions and materials of biological interest.


Dependence of interferon induction on nucleic acid conformation. UV and circular dichroism characteristics of duplex analogs belonging to the (A)n-(U)n and (I)n-(C)n series were determined to assign qualitatively the nature of conformational differences caused by 5-pyrimidine and c7 purine substitutions in such duplexes. Evidence is presented which shows that 5-pyrimidine substitution by bromine or methyl changes the duplex conformation of both series in a similar way, if at all. A c7 substitution in the purine ring affects the duplex conformation of the members in the same series similarly, but the conformational change appears to be different for the two series. To wit, it is proposed that in the duplexes the effect of the change (A)n leads to (c7A)n is an increase of the positive base tilt, whereas the change (I)n leads to (c7I)n causes a decrease where (c7A)n is poly (7-deazaadenylic acid) and (c7I)n is poly(7-deazainosinic acid), respectively. Poly(5-bromocytidylic acid) (br5C)n proved to be useful as  a sensor strand for the intepretation of the spectroscopic data. The circular dichroism findings correlate well with observations made earlier on the interferon inducing ability for such duplexes, namely, duplexes based on the (c7A)n are inactive as interferon inducers, whereas duplexes based on (c7I)n are potent inducers. Furthermore, a 5-pyrimidine substitution does not substantially affect the interferon inducing ability, unless the thermal stability of the analog becomes critical, as in the case of (A)n-(br5U)n. Thus, this study provides the first evidence to link the interferon-inducing ability of a nucleic acid to a defined physical parameter of double helix, and reinforces the concept that interferon induction is dependent on the recognition of a particular spatial and steric organization of a double-stranded RNA.


Crystal structure of a complex between lumiflavin and 2,6-diamino-9-ethylpurine: a flavin adenine dinucleotide model exhibiting charge-transfer interactions. The x-ray structure of the deep red crystalline complex lumiflavin-2,6-diamino-9-ethylpurine has been determined. The flavin and adenine derivatives form hydrogen-bonded base pairs of the Watson-Crick type. The molecules in the crystal also associate via extensively overlapped flavin/adenine and flavin/flavin stacking interactions in which there are several contacts that are closer than van der Waals distances. This, together with the red color of the crystals, is indicative of the formation of a charge-transfer complex.


Nuclear magnetic resonance description of molecular motion and phase separations of cholesterol in lecithin dispersions. Proton-enhanced 13C nuclear magnetic resonance is used to obtain signals from labeled cholesterols in lecithin dispersions. The [26-(13)C]cholesterol resonance indicates that the aliphatic tail of the molecule undergoes reorientation fast enough to average completely the chemical shift anisotropy. In contrast, [4-(13)C]cholesterol signals are characteristic of limited anisotropic reorientation. The resonances from the 4 position are sensitive to the temperature-concentration phase diagram. A phase boundary is observed at about 20 mole percent cholesterol.


Role of proteolytic enzymes in biological regulation (a review). Many enzymes, hormones, and other physiologically active proteins are synthesized as inactive precursors (zymogens) that are subsequently converted to the active form by the selective enzymatic cleavage (limited proteolysis) of peptide bonds. The ultimate agency of activating enzymatic function is limited proteolysis, either in a single activation step or in a consecutive series (cascade). The specificity of each activation reaction is determined by the complementarity of the zymogen substrate and the active site of the attacking protease. The sequence of consecutive activation reactions is regulated by the specificity of each enzyme, whereas the degree of amplification of the initial stimulus is determined by the efficiency of each activating step. Zymogen activation produces a prompt and irreversible response to a physiological stimulus, and is capable of initiating new physiological functions. Typical examples are the precesses of blood coagulation, fibrinolysis, complement activation, hormone production, metamorphosis, fertilazation, supra-molecular assembly, and digestion. The zymogens of the pancreatic serine proteases, in particular, have served as models for detailed studies of the nature of the molecular changes that are involved in the dramatic increase in enzymatic activity that ensues upon limited proteolysis of the zymogen.


Synthesis and activities of neurotensin, and its acid and amide analogs: possible natural occurrence of [Gln4]-neurotensin. It was considered, a priori, that the isolation of the tridecapeptide, neurotensin, might have inadvertently sllowed the hydrolysis of either the [Gln4]- or the [Leu13-NH2]-moieties. Neurotensin and its three acid and amide analogs, i.e., [Gln4]-neurotensin, neurotensin-NH2, and [Gln4]-neurotensin-NH2 were synthesized. Neurotensin and [Gln4]-neurotensin were indistinguishable by the hypotensive assay, hyperglycemic assay, contraction of the ileum, and radioimmunoassay. Neurotensin-NH2 and [Gln4]-neurotensin-NH2 showed less than 1% of these neurotensin activities. Present information does not elucidate whether the glutamic acid residue in position 4 of neurotensin in situ is present as Glu4 or as Gln4. At high levels, neurotensin released the luteinizing hormone, follicle stimulating hormone, and thyrotropin; [Gln4]-neurotensin-NH2 released thyrotropin, and [Gln4]-neurotensin released luteinizing hormone and follicle stimulating hormone, but these activities do not appear biologically significant.


Investigation of phase transitions of lipids and lipid mixtures by sensitivity differential scanning calorimetry. High sensitivity differential scanning calorimetry is applied to the study of the thermotropic behavior of mixtures of synthetic phospholipids in multilamellar aqueous suspensions. The systems dimyristoylphosphatidylcholine dipalmitoylphosphatidylcholine, and  dimyristoylphosphatidylethanolamine-distearoylphosphatidylcholine, although definitely nonideal, exhibit essentially complete miscibility in both gel and liquid crystalline states, while the system dilauroylphosphatidylcholine-distearoylphosphatidylcholine is monotectic with lateral phase separation in the gel state. Comparison of the observed transition curves with theoretical curves calculated from the calorimetrically determined phase diagrams supports a literal interpretation of the phase diagrams.


Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Viroids are uncoated infectious RNA molecules pathogenic to certain higher plants. Four different highly purified viroids were studied. By ultracentrifugation, thermal denaturation, electron microscopy, and end group analysis the following features were established: (i) the molecular weight of cucumber pale fruit viroid from tomato is 110,000, of citrus exocortis viroid from Gynura 119,000, of citrus exocortis viroid from tomato 119,000 and of potato spindle tuber viroid from tomato 127,000. (ii) Viroids are single-stranded molecules. (iii) Virods exhibit high thermal stability, cooperativity, and self-complementarity resulting in a rod-like native structure. (iv) Viroids are covalently closed circular RNA molecules.


Mechanism of action of carboxypeptidase A in ester hydrolysis. The reaction of carboxypeptidase A (peptidyl-L-amino-acid hydrolase; EC 3.4.12.2) with the specific ester substrate O-(trans-p-chlorocinnamoyl)-L-beta-phenyllactate has been investigated in the temperature range 25 degrees to -40 degrees with use of organic-aqueous cosolvent mixtures. In the subzero temperature range the hydrolysis reaction is characterized by a biphasic decrease in absorbance specific for the substrate. The kinetic data can be unambigously analyzed as two consecutive first-order reactions with formation of a covalent acyl-enzyme intermediate. Deacylation of the covalent intermediate is shown to be rate-limiting in the subzero temperature range, and near -60 degrees it is sufficiently stable for spectral characterization. Consideration of the structure of the active site and of the catalytically functional residues of the enzyme leads to the conclusion that the intermediate is a mixed anhydride in which the gamma-carboxylate of glutamate-270 is acylated by the substrate. The temperature dependence of the rate constants of the acylation and deacylation steps explains why the intermediate of this enzyme-catalyzed reaction is observed only at low temperatures.


(+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo (a)pyrene: a potent skin carcinogen when applied topically to mice. (+/-)-trans-7,8-Dihydroxy-7,8-dihydrobenzo[a]-pyrene, a known metabolite of benzo [a]pyrene, has been tested for carcinogenic activity on mouse skin by topical application of 0.15 or 0.30 mumol every 2 weeks for 60 weeks. At the low dose (0.15 mumol), the compound was equipotent to the parent hydrocarbon, benzo[a]pyrene, and considerably more potent than its metabolic precursor, benzo[a]pyrene 7,8-oxide, in eliciting tumors, as determined by both the onset of tumors and the total number of animals developing carcinomas. Application of 7,8-epoxy-,8,9,10-tetrahydrobenzo[a]pyrene (0.30 mumol every 2 weeks), a compound related to the carcinogenic benzo[a]pyrene 7,8-oxide but with the double bond removed from the 9,10-position of the molecule, did not elicit any tumors. The above results indicate that the (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene is a more proximate carcinogen than benzo[a]pyrene 7,8-oxide and that the carcinogenicity of benzo[a]pyrene 7,8-oxide and (+/-)trans-7,8-digydrobenzo[a]pyrene may be due to metabolic conversion of these compounds to the highly reactive and mutagenic stereoisomers of 7,8-digydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.


Photoreceptor pigment that induces differentiation in the slime mold Physarum polycephalum. An extract of small molecules (molecular weight less than 500) of the slime mold Physarum polycephalum undergoes a shift in ultraviolet-visible absorption spectrum upon illumination. This illumination also confers on the extract the ability to induce sporulation when injected into a starved, unilluminated slime mold. The spectral shift and appearance of the sporulation-inducing activity both occur regardless of whether the illumination is carried out on an intact slime mold or on the plasmodium-free extract itself. Thin-layer chromatography resolves the slime mold extract into four major visible fractions. One of these has high sporulation-inducing activity after illumination in vitro.


A plasmid cloning vehicle allowing regulated expression of eukaryotic DNA in bacteria. We have constructed a plasmid cloning vehicle in which transcription of inserted heterologous DNA fragments can be regulated by a defined bacterial operator and promoter. The lambda plac 5 EcoRIDNA fragment containing the operator, promoter, and beta-galactosidase gene of the lactose operon was linked to the ColE1 derivative plasmid pSF2124, creating a plasmid designated pBGP100, pBGP100 contains one EcoRI site at the lac DNA/pSF2124 DNA junction and another at the lambda DAN/pSF2124 DNA junction. We deleted the latter EcoRI site to generate a plasmid (pBGP120) retaining a single EcoRI site at the lac DNA/nSF2124 DNA junction. To determine whether DNA introduced at the EcoRI site of pBGP120 was expressed under lactose control, we inserted the EcoRI fragment containing 28S ribosomal DNA of Xenopus laevis, creating the hybrid plasmid pBGP123. RNA-DNA hybridization of pulse-labeled RNA from cells containing pBGP123 showed that induction of the lac operon increases the percentage of labeled RNA complementary to Xenopus 28S DNA about 9-fold. This vehicle may be of use for production of eukaryotic gene products in bacteria.


Reconstitution of intramembrane particles in recombinants of erythrocyte protein band 3 and lipid: effects of spectrin-actin association. The integral membrane protein Band 3 of the human erythrocyte, either purified or in a crude Triton X-100 extract of ghosts, was combined with egg lecithin in a cholate solution. During dialysis to remove cholate, lipid bilayer vesicles formed in which Band 3 existed as a dimer and in which intramembrane particles indistinguishable from those in the native membrane were exposed by freeze-fracturing. The recombinant vesicles were stable in both high and low salt concentrations, sedimented at a density that increased in prportion to their protein content, and bound spectrin-actin extracted from erythrocyte ghosts. When spectrin-actin was associated with the vesicles, the behavior of the recombinant intramembrane particles simulated that of the erythrocyte ghost intramembrane particles: they were dispersed at pH 7.6 and aggregrated at pH 5-5.5. Thus, some of the characteristics of the native membrane have been reconstituted in the recombinant.


DNA methylation in adenovirus, adenovirus-transformed cells, and host cells. DNAs of adenovirus type 2 and type 12 contain low amounts of methylated bases (0.01 and 0.02% N6-methyl-adenine per adenine, if any, and 0.04 and 0.06% 5-methylcytosine per cytosine for type 2 and type 12, respectively), whereas the DNA of the mammalian host cells contains much more 5-methylcytosine (3.57% for human KB cells). The DNA of hamster cells transformed by adenovirus type 12 contains 3.11 and 3.14% 5-methycytosine (HA12/7 and T627 cells, respectively), whereas the DNA from untransformed hamster cells (BHK21 cells) contains 2.22% 5-methylcytosine. In the DNA of human and hamster cells, little, if any, N6-methyladenine was detected. Methylation of DNA was determined by a sensitive method based on two consecutive steps of two-dimensional thin-layer chromatography of the radioactively labeled DNA bases. By this procedure the detection limits of 5-methylcytosine and N6-methyladenine could be lowered to 0.01% per main base.


5-bromodeoxyuridine-DNA strand symmetry and the repair of photolytic breaks in Chinese hamster cell chromosomes. Experiments described in this report quantiate the black light sensitivities of Chinese hamster lung (CHL) cells containing BrdUrd-DNA of defined composition. Cesium chloride equilibrium gradient centrifugation provides estimates both of the percent thymidine replacement by BrdUrd and of the symmetry (unifilar versus bifilar) of BrdUrd incorporation into the chromosomal DNA duplexes. Radiation damage to BrdUrd-substituted CHL cell DNA and its repair in situ also have been assessed by alkaline sucrose gradient sedimentation. We observe that animal cell sensitivities to visible light (300-400 nm wavelength) depend markedly upon the symmetries of BrdUrd-substitution within the cells Dna. Cells that contain only unifilar BrdUrd-DNA are resistant to black light, whereas cells that contain bifilar BrdUrd-DNA are extremely photosensitive. The former cell populations repair single-stranded  nicks (breaks in phosphodiester bonds) in their DNA within 24 hr of irradiation; the latter cell populations, however, are not able to repair light-induced, double-stranded breaks in their DNA.


Selective digestion of transcriptionally active ovalbumin genes from oviduct nuclei. Analysis of the DNA of isolated nucleosomes suggests that virtually all genomic DNA sequences are organized in this basic chromatin subunit. In this report, we demonstrate that although histones reside on the transcriptionally active ovalbumin genes in the oviduct, the organization of proteins about this gene renders it highly sensitive to deoxyribonuclease I (deoxyribonucleate 5'-oligonucleotidohydrolase, EC 3.1.4.5). Treatment of oviduct nuclei from the laying hen with pancreatic deoxyribonuclease I results in the preferential digestion of over 70% of the ovalbumin sequences when only 10% of the total nuclear DNA has been solubilized. Treatment of liver nuclei does not reveal selective sensitivity of these genes to DNase I. Furthermore, regions of DNA not actively transcribed, such as the endogenous leukosis virus genes in the oviduct, are not selectively degraded by this enzyme. Similar digestions with micrococcal nuclease, however, reveal no specific digestion of transcriptionally active chromatin. These data confirm the observations of H. Weintraub and M. Groudine [(1976) Science 193, 848-856] and suggest we are dealing with an aspect of structure that may be necessary to permit transcription of the chromatin complex.


A method for the modulation of membrane fluidity: homogeneous catalytic hydrogenation of phospholipids and phospholipids and phospholipid-water model biomembranes. The fatty acids associated with phospholipids of cell membranes, and particularly their degree of unsaturation, contribute to the fluidity of their structure and hance determine many of their biological properties. We describe a technique for modulating membrane fluidity which consists of hydrogenating the unsaturated double bonds of membrane phospholipids. This has been accomplished using a homogeneous catalyst. The process has been applied to phospholipids in organic solvents, to phospholipids dispersed as multibilayers in aqueous systems, and also to sonicated preparations of phospholipids arranged as single bilayer vesicles. Preliminary experiments have also been performed with biological membranes. These results indicate that the process of homogeneous catalysis for the modulation of lipid fluidity of biological cell membranes may have considerable future biological and biochemical application.


Activation of chromatin by acetylation of histone side chains. The ability of calf thymus chromatin to support DNA-dependent RNA synthesis is markedly increased by modification of the histones with acetic anhydride. The extent of chemical acetylation of histones H2a, H2b, H3, and H4 required for the increase of template activity of the chromatin is within that which can be achieved enzymatically in the cell. The evidence suggests that the acetylation of histone side chains stimulates the rate of chain elongation during transcription of chromatin.


Changes in levels of cellular retinol- and retinoic-acid-binding proteins of liver and lung during perinatal development of rat. Cellular retinol-binding protein and cellular retinoic-acid-binding protein, canditates for mediating the action of vitamin A, were found to be present in tissues of the fetal rat. Cellular retinol-binding proteins were still present in most tissues of the adult, but the retinoic-acid-binding protein was not detected in some, including lung, liver, intestine, and kidney. During perinatal development of lung the level of cellular retinol-binding protein remained relatively constant while the level of the cellular retinoic-acid-binding protein peaked at 10 days postnatally, then declined. It was not detectable in lung tissue from 21-day-old rats. In liver, however, the retinoic-acid-binding protein was not detectable later than 5 days postnatally, while the level of the cellular retinol-binding proteinrose sharply near birth, declining only after 21 days to the lower adult levels. The variations observed in the levels of the two binding proteins suggest different and changing requirements for retinol and retinoic acid in organ development and maturation.


Presence of diadenosine 5',5''' -P1, P4-tetraphosphate (Ap4A) in mamalian cells in levels varying widely with proliferative activity of the tissue: a possible positive "pleiotypic activator". An accurate assay of diadenosine 5',5'''- P1,P4-tetraphosphate [A(5') pppp(5')A], which was shown to be formed in vitro in the backreaction of the amino acid activation step, has been developed in various cell lines in culture and in normal mouse liver or hepatoma in vivo. Use of radioactive labeling of acid-soluble nucleotides to high specific activity  followed by chromatographic separation techniques yielded levels of Ap4A varying from 5 to 0.05 muM (from 30 pmol/mg of protein to 0.15 pmol), depending on the doubling time of the cell line or the proliferative state of the cells. The levels of Ap4A incells is inversely related to their doubling time, varying from 0.1  X 10(-4) of the cellular ATP levels in slowly growing cells to 20 X 10(-4) of the ATP levels of cells with rapid doubling times. The steady-state levels of ATP of different cell lines, although showing some fluctuations, are not related to the doubling time of the cells. Arrest of cellular proliferation by serum deprivation or amino acid starvation, which does not alter the cellular ATP levels more than 2-fold, does nevertheless cause a decrease of 30 to 50-fold in the Ap4A levels. Inhibition of protein synthesis by pactamycin or puromycin, or inhibition of DNA synthesis by hydroxyurea, leads to a more dramatic decrease of 50 to 100-fold in intracellular Ap4A levels. The metabolic lability of Ap4A is also demonstrated by its rapid depletion after decreases in the ATP/ADP ratio. The possibility of Ap4A being a metabolic "signal nucleotide" that is formed at the onset of protein synthesis and is active in positive growth regulation (positive pleiotypic activation) is discussed.


Dynamic properties of isolated acetylcholine receptor protein: kinetics of the binding of acetylcholine and Ca ions. Kinetic and thermodynamic constants for elementary steps associated with the interaction of acetylcholine (AcCh) and Ca with isolated AcCh receptor from Torpedo californica have been determined by chemical relaxation spectrometry. Murexide as used as a Ca indicator to monitor changes in Ca bound to the AcCh receptor. In the presence of AcCh this technique permits an indirect monitoring of AcCh binding, because the AcCh and the Ca binding reactions are competitively coupled. A temperature-jump perturbation in the Camurexide-AcCh receptor system induces a spectrum of relaxation processes characterized by at least three relaxation times: tau1 = 5 (+/-1) msec; tau2 = 35 (+/-5) msec; and tau3 = 300 (+/-30) msec. In the presence of AcCh, the Ca relaxation spectrum is altered in a characteristic way. A formalism is developed to describe the normal mode relaxation times of the coupled reaction system in terms of total concentrations of both AcCh and receptor binding sites. The analysis also allows one to determine the stoichiometry of the reactions involved or to estimate a molecular weight of the AcCh receptor. The kinetic data suggest that the reaction of AcCh with receptor proceeds in at least two steps. The rate constant of the association of AcCh with receptor was found to be 2.4(+/-0.5) X 10(7) M-1 sec-1 at 23.5 degrees, 0.1 M NaCl, 50 mM Tris-HCl, pH 8.5. Reaction schemes consistent with the present kinetic data are discussed in terms of physiocochemical model that accounts for the rapid transient conductivity changes in excitable membranes during nerve and muscle excitation.


Analogue solution for electrical capacity of membrane-covered cubes in cubic array at high concentration. Earlier measurements have shown that the equations derived for the resistance of suspension of spheres apply up to a volume concentration of 100% for close-packing forms. They have also shown, by a resistance-capacitance analogue, that they apply for the capacity of a close-packing of membrane-covered square cylinders in square array, approximating muscle and nerve. The present work is an extension of the two-dimensional to a three-dimensional array of membrane-covered cubes in a cubic array. It is found by measurements of a three-dimensional electrolytic analogue that the capacitance is indeed expressed by an extension of the analytic solution at low concentrations up to 100% volume concentration of the membrane-covered form, such as epithelial tissues. There is thus at least one example each of two-and three-dimensional forms which conform to the low concentration analysis up to 100% volume and so give a basis for the extensions to other and more complicated forms to complete a survey to work begun by Fricke in 1923.


Nuclear magnetic resonance studies of the interaction of general anesthetics with 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine bilayer. Sonicated 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine forms liposomes. Studies by Fourier transform proton magnetic resonance of the interaction of these bilayers with some general anesthetics, i.e., chloroform, halothane, methoxyflurane, and enflurane, show that the addition of a  general anesthetic to the liposomes and raising the temperature have a similar effect in cuasing the fluidization of the bilayer. General anesthetics act on the hydrophilic site (choline group) in clinical concentrations and then diffuse into the hydrophobic region with the addition of larger amount of anesthetics. There is evidence that the lecithin choline groups are involved in the interaction with protein and that the general anesthetics change the conformation of some polypeptides and proteins. We conclude that the general anesthetics, by increasing the motion of positively charged choline groups and negatively charged groups in protein, weaken the Coulomb-type interaction and cause the liprotein conformational changes.


Colicin E2 is DNA endonuclease.

Colicin E2 is DNA endonuclease. Colicin E2 purified by conventional methods contains a tightly bound low-molecular-weight protein, as has been found with purified colicin E3 [Jakes,N.&Zinder,N.D.(1974) Proc. Natl. Acad. Sci. USA 71, 3380-3384]. Such E2 preparations do not cause DNA cleavage in vitro. After separation from the low-molecular-weight protein, colicin E2 retained the original in vivo killing activity, and in addition showed a high activity in vitro in cleaving various DNA molecules, such as a ColE1 hybrid plasmid and DNAs from Escherichia coli, lambda phage, chiX174 phage, and simian virus 40. The low-molecular-weight protein ("E2-immunity protein") specifically prevented this in vitro DNA cleavage reaction, i.e., had an "immunity function." The results demonstrate that colicin E2 itself is a DNA endonuclease and explain the in vivo effects caused by E2 in sensitive cells as well as the mechanism of immunity in E2-colicinogenic cells.


Actin-like filaments amd membrane rearrangement in oxyntic cells. The secretory pole of vertebrate oxyntic cells possesses two distinct membrane systems: the apical plasma membrane which presents numerous infoldings, microvilli and processes, and a complex tubulovesicular system located in close proximity to the plasma membrane. These two membrane systems are generally believed to be interconvertible in relation to the functional state of the cell. To determine the role that filaments may play in the interconversion process, the secretory pole of rat and toad oxyntic cells was examined by electron microscopy under conditions designed to demonstrate filamentous structures, i.e., slight cellular swelling and incubation with heavy meromyosin. Filaments 50-80 A in diameter are present in close association with the plasma membrane to which they are connected by regularly spaced bridges. Heavy meroxyosin-treated material reveals "decorated" filaments in topographically corresponding locations. No filaments are seen in association with membranes of the tubulovesicular system. These findings suggest that association with actin-like filaments is a step in the translocation of membranes from the tubulovesicular system to the plasma membrane.


Collagen fibrillogenesis: intermediate aggregates and suprafibrillar order. Polymerization of collagen in vitro has been studied with the electron microscope at early time points of fibril assembly. We have found morphologically distinct stages of aggregation, which we suggest represent successive steps in fibril formation. Linear growth of the fibril appears to occur by the tandem addition of aggregates to each other and subsequently to the ends of a subfibril; lateral growth occurs by the entwining, like a rope, of these subfibrils. Fibrillogenesis is also accompanied by extensive development of suprafibrillar order in which various patterns of parallel, spiral, and orthogonal sets of fibrils were frequently observed.


Tissue interaction in androgen response of embryonic mammary rudiment of mouse: identification of target tissue for testosterone. In the androgen response of the embryonic mammary rudiment of the mouse, both gland epithelium and surrounding mesenchyme are visibly involved. The question whether this is due to a direct action of testosterone on both tissues was investigated in experimental combination of mammary epithelium and mammary mesenchyme, derived either from normal or from androgen-insensitive (XTfm/Y) embryos. A typical androgen response occurred in combinations of androgen-insensitive epithelium with normal mesenchyme, whereas all combinations of normal epithelium with androgen-insensitive mesenchyme failed to respond. It is therefore concluded that only the mesenchyme of the mammary rudiment is the target tissue for testosterone, and that all changes in the gland epithelium, including its necrosis, are secondarily caused by testosterone-activated mesenchymal cells.


Quantized generation time in mammalian cells as an expression of the cellular clock. The distribution of possible generation times in mammalian cells does not appear to be continous within the limits of range for each cell type; rather, generation time is quantized in multiples of 3-4 hr. Synchronous cultures of Chinese hamster V79 cells were prepared using manual and automated methods to select and stage mitotic cells. Using synchronous cultures and time-lapse video tape microscopy, it was possible to show that generation times within a population of mitotically selected cells normally disperse in a quantized fashion, with intervals of 3-4 hr occurring between bursts in division. In addition, at temperatures above 37 degrees, V79 cells have a 7.5-8.5 hr modal cell cycle, while at temperatures from 36.5 degrees to 33.5 degrees the modal cell cycle is 11-12 hr long. A survey of the synchrony literature reveals that the tendency to preferred generation times holds between cell lines. The distribution of modal generation times from a variety of different cell types forms a series with a similar interval but with a greater range of values than that observed here for V79 cells. To satisfy the published data and the work presented here, I propose a subcycle, Gq, which has a traverse time equal to the period of the clock. The period appears to be fixed at close to the same value in all mammalian somatic cells. The timekeeping mechanism appears to be temperature compensated, since the time required to traverse Gq is constant at temperatures between 34 degrees and 39 degrees. It is suggested that cell cycle time increases at lower temperatures, lower serum concentration, and high cell densitite because the number of rounds of traverse through Gq increases.


Subcellualr distribution of protein carboxymethylase and its endogenous substrates in the adrenal medulla: possible role in excitation-secretion coupling. Protein carboxymethylase (S-adenosyl-L-methionine:protein O-methyltransferase, EC 2.1.1.24) transfers a methyl group from S-adenoxyl-L-methionine to carboxyl side chains of proteins to form labile protein-methyl esters which, thus, neutralize negative charges. This enzyme was examined for its possible participation in excitation-secretion coupling in the adrenal medulla. Protein carboxymethylase has a specific activity several times higher in the adrenal medulla than in the adrenal cortex; also, the medulla has a higher concentration of methyl-acceptor proteins. In the adrenal medulla, 97% of the enzyme was localized in the cytosol. Of the various subcellular fractions of the medulla, the catecholamine-containing chromaffin vesicles had the highest concentrations of substrat(s) for protein carboxymethylase. Carboxymethylation of proteins in intact chromaffin vesicles results in stripping of methylated protein(s) from the membranes. Thus, protein carboxymethylase appears to be involved in the neutralization of charges on the surface of chromaffin vesicles and in the release of surface proteins; both phenomena are likely to be required for exocytosis.


Tubulin requires tau for growth onto microtubule initiating sites. Tubulin purified by phosphocellulose chromatography and free of accessory proteins will not form microtubules in the absence or presence of microtubule initiating sites (flagellar microtubules). The capacity for growth onto pre-existing "seeds" can be restored by the addition of small quantities of partially purified tau protein. Larger quantities restore the capacity for spontaneous assembly. These results suggest that tubulin requires tau for both initiation and growth of microtubules and that tau is incorporated into the microtubule throughout its length.


Simultaneous synthesis of types I and III collagen by fibroblasts in culture. Specific antibodies against types I and III collagens and procollagens were used to localize these proteins in cultured human cells. These studies indicate that the same cell makes both proteins. No type III procollagen synthesis was observed in cells from two patients with two patients with the Ehlers-Danlos type IV syndrome.


Embryonal carcinoma antigen and the T/t locus of the mouse. The presence of the F9 antigen and of four other antigens related to the T/t locus of the mouse was investigated by immunofluorescence on preimplantation embryos. In morulae heterozygous for any of these t haplotypes, both the appropriate t antigen and the F9 antigen are expressed. The F9 antigen segregates among the progeny of crosses producing embryos homozygous for some (tw32 and tw5) but not for other haplotypes. It is concluded that (i) whatever the time of action of a t haplotype, its corresponding antigen is expressed during cleavage and (ii) the F9 antigen is specified by a gene(s) in the region of the T/t locus.


Clustering and endocytosis of membrane receptors can be induced in mature erythrocytes of neonatal but not adult humans. Concanavalin A (Con A) is taken up by endocytosis in mature erythrocytes of newborn humans but not in adult red cells. Thin sections of neonatal cells incubated with ferritin-conjugated Con A at 37 degrees show ferritin clusters on invaginations at the surface and in intracellular vesicles, but such invaginations and vesicles are absent with adult cells. The endocytosis induced by ferritin-conjugated Con A is inhibited at 0 degrees, and by methyl-alpha-D-mannopyranoside at 37 degrees. Succinylation of Con A, which is known to convert it from the tetrameric to dimeric form, renders Con A inactive in cell agglutination and endocytotic vesicle formation, presumably by reducing the number of oligosaccharide chains simultaneously bound by a single Con A molecule. Ferritin-conjugated succinyl Con A binds to neonatal erythrocytes but does not induce endocytosis; if, however, antibodies to ferritin are now added, endocytosis occurs. These results are consistent with a greater lateral mobility of at least a fraction of Con A recptors in the membrane of the intact neonatal erythrocyte compared to the adult. The results also support the hypothesis that the clustering of receptors is obligatory for endocytosis to occur. No discernible difference was found in the sodium dodecyl sulfate/polyacrylamide gel patterns of the membrane proteins of the neonatal and adult cells.


Active cell edge and movements of concanavalin A receptors of the surface of epithelial and fibroblastic cells. Movements of the receptors of concanavalin A on various parts of the surfaces of substrate-attached cells were compared. Cultured mouse embryo cells of several types were used: epithelial kidney cells and normal and transformed fibroblasts. Initial distribution of receptors was random on the cells of all types. Binding of concanavalin A induced patching of its receptors on all the cell parts. In contrast, directional centripetal movement of receptors was observed only on the surface of certain cell parts, namely, only the surface of peripheral lamellar cytoplasm was cleared of the receptors. Clearing was always initiated in the zone of lamellar cytoplasm located near active cell edges. In epithelial sheets, clearing was not observed on the surface of central cells that had no lamellar cytoplasm. Concanavalin A receptors on the cleared areas of cell surface were gradually restored after the end of incubation. It is suggested that anchoring of the patches of membrane receptors by cortical microfilaments is possible only on the surface of pseudopods and of lamellar cytoplasm but not on the surface of other cell parts. Besides receptor movements, this hypothesis may be explain differences in the adhesive properties of various parts of the cell surface.


Differential labeling of the cell surface of single ciliary ganglion neurons in vitro. Cationic ferritin binds in a time and concentration dependent manner to all surfaces of ciliary ganglion neurons in culture except "mounds" and "veils". In chase experiments, bound ferritin clears from the cells surfaces and forms larger and larger patches, even at low temperatures. Binding of cationic ferritin is inhibited by poly-L-lysine, potentiated by poly-L-glutamate, and not affected by neruaminidase (acylneuraminyl hydrolase, EC 3.2.1.18), hyaluronidase (hyaluronoglucosidase, hyaluronate 4-glycanhydrolase, EC 3.2.1.35), or chondroitin ABC lyase (EC 4.2.2.4).


Survival of fetal rat pancreases frozen to -78 and -196 degrees. Transplantation of pancreases may have clinical utility in the treatment of diabetes, for it has been shown that chemically induced diabetes in rats can be reversed by the transplantation of greater than or equal to four syngeneic fetal pancreases. Allogeneic transplants produce serious immunological problems, but the problems could be ameliorated if tissue-typed organs could be stored in the frozen state. Unfortunately, nearly all attempts to freeze organs have failed. Nevertheless, recent developments in the physical-chemical analysis of freezing injury and its successful application to the freezing of mammalian embryos encouraged us to attempt the freezing of 16 1/2- to 17 1/2-day intact fetal pancreases. The analysis indicated that to achieve success pancreases would have to be cooled less than 1 degree/min and diluted extremely slowly after thawing. Experiments with embryos and red cells indicated that high survivals might require high concentrations of protective solutes and slow warming. These predictions were accurate. After freezing to -78 or -196 degrees and thawing under optimal conditions, the fetal pancreases synthesized 80-100% as much protein as unfrozen controls and they yielded viable allografts. Optimal conditions included suspension in 2 M dimethylsulfoxide, freezing at 0.3 degrees/min, and slow dilution to preclude osmotic shock.


Growth of human diploid fibroblasts in the absence of glucose utilization. Normal human diploid fibroblasts were able to undergo one to two cell divisions without glucose utilization in Eagle's minimum essential medium plus 10% dialyzed fetal calf serum if the medium was supplemented with hypoxanthine, thymidine, and uridine (supplemented medium termed HTU-MEM). Under these conditions, the added purine and pyrimidines were required for nucleic acid synthesis, as shown by the inability of Lesch-Nyhan fibroblasts to grow in HTU-MEM. Normal human diploid fibroblasts continued to produce lactate in HTU-MEM, but at a greatly reduced rate. Since cells grew in HTU-MEM without glucose utilization, the probable energy and carbon source was glutamine, which is present in relatively high concentration. Furthermore, the rate of glutamine utilization per cell division was 2-fold greater in HTU-MEM than in medium with 5.5 mM glucose. These results suggest that glutamine can be a major energy source for cells grown in vitro.